Hybrid coronary revascularization in the era of drug-eluting stents

Left internal mammary artery to left anterior descending coronary artery bypass grafting integrated with percutaneous coronary angioplasty (hybrid procedure) offers multivessel revascularization with minimal morbidity in high-risk patients. This is caused in part by the avoidance of cardiopulmonary bypass-related morbidity and manipulation of the aorta coupled with minimally invasive techniques. Hybrid revascularization is currently reserved for particularly high-risk patients or those with favorable anatomic variants however, largely because of the emergence of off-pump coronary artery bypass grafting, which permits more complete multivessel revascularization, with low morbidity in high-risk groups. The wider introduction of hybrid revascularization is limited chiefly by the high number of repeat interventions compared with off-pump coronary artery bypass grafting, which occurs because of the target vessel failure rate of percutaneous coronary intervention. Other demerits are the costs and logistic problems associated with performing two procedures with differing periprocedural management protocols. Recently, drug-eluting stents have reduced the need for repeat intervention after percutaneous coronary intervention, and this has raised the possibility that the results of hybrid revascularization may now equal or even better those of off-pump coronary artery bypass grafting. Although undoubtedly effective at reducing in-stent restenosis, drug-eluting stents will not address the issues of incomplete revascularization or the logistic problems associated with hybrid. Uncertainty regarding the long-term effectiveness of drug-eluting stents in many patients, as well as their high cost when compared with those of off-pump coronary artery bypass grafting surgery, also militates against the wider introduction of hybrid revascularization.     

Transcranial Magnetic Stimulation: Use of Motor Evoked Potentials in the Evaluation of Surgically Induced Spinal Cord Ischemia

Abstract

We evaluated transcranial magnetic stimulation producing motor evoked potentials (TMS MEP) as a method to detect spinal cord ischemia during surgery for thoracoabdominal aneurysms. Four groups of swine were subjected to different types of surgically-induced ischemia. TMS MEP and neurological function were assessed at baseline, immediately after the ischemic insult and after four hours of reperfusion/post-ligation. Cross-clamping of the aorta in groups A & B resulted in the disappearance and subsequent reappearance of TMS MEP with significantly prolonged latencies in most animals and variable neurological function. Ligation of intercostal arteries produced no changes in TMS MEP or neurological function (group C). However, after ligation of intercostal and lumbar arteries, group D demonstrated no reappearance of TMS MEP and severe neurological deficits. TMS MEP can provide rapid detection of global spinal cord ischemia and can also predict local devascularization injury. (J Spinal Cord Med 1997; 20:395-401)     

Single-Incision Laparoscopic Cholecystectomy: Do Patients Care?

Introduction  

Single-incision approaches to laparoscopic cholecystectomy typically involve increasing the size of the umbilical incision and eliminating three smaller incisions, but it is not intuitive that patients would view this as a benefit. We hypothesize that when patient satisfaction with standard laparoscopic cholecystectomy is assessed, most dissatisfaction will be linked to the umbilical incision and, given the option, patients would actually wish to eliminate this incision.     

Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation

BACKGROUND: Epidural morphine has proven analgesic efficacy in the postoperative period and is widely used. This study evaluated the efficacy of extended-release epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA; SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery. METHODS: Patients (n = 200) scheduled to undergo total hip arthroplasty were randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After surgery and after asking for pain medication, patients had access to intravenous patient-controlled analgesia fentanyl for breakthrough pain as needed. Postoperative intravenous patient-controlled analgesia fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient and surgeon ratings of pain control, and adverse events were recorded. RESULTS: All EREM dosages reduced the mean (+/- SD) fentanyl use versus placebo (510 +/- 708 vs. 2,091 +/- 1,803 microg; P < 0.0001) and delayed the median time to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had significantly improved pain control at rest through 48 h postdose (area under the curve [0-48 h]) compared with placebo (P < 0.0005). More EREM-treated patients rated their pain control as good or very good compared with placebo (at 24 h: 90 vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at 48 h (P < 0.05). The safety profile of EREM was consistent with that of other epidurally administered opioid analgesics. CONCLUSIONS: EREM provided significant postoperative pain relief over a 48-h period after hip surgery, without the need for indwelling epidural catheters.     

Repeating an abnormal prostate-specific antigen (PSA) level: how relevant is a decrease in PSA?

To examine the practice of repeating an abnormal prostate-specific antigen (PSA) level before proceeding to prostate biopsy, we assessed the pattern of PSA change following an initially raised (>or=4.0 ng ml(-1)) PSA, and the relationship of this to prostate cancer diagnosis. In 7052 men, 71.2% with initially raised PSA had a reduction in PSA, with values <4.0 ng ml(-1) in 37.8%. A total of 43.0% of men with prostate cancer showed a PSA decrease below their baseline level. Short-term decreases in PSA may occur in men with prostate cancer, including high-grade cancer, and so should not influence the decision to proceed to prostate biopsy.     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.     

A new teaching model for resident training in regional anesthesia

The adequacy of resident education in regional anesthesia is of national concern. A teaching model to improve resident training in regional anesthesia was instituted in the Anesthesiology Residency in 1996 at Duke University Health System. The key feature of the model was the use of a CA-3 resident in the preoperative area to perform regional anesthesia techniques. We assessed the success of the new model by comparing the data supplied by the Anesthesiology Residency to the Residency Review Committee for Anesthesiology for the training period July 1992-June 1995 (pre-model) and the training period July 1998-June 2001 (post-model). During the 3-yr training period, the pre-model CA-3 residents (n = 12) performed a cumulative total of 80 (58-105) peripheral nerve blocks (PNBs), 66 (59-74) spinal anesthetics, and 133 (127-142) epidural anesthetics. The CA-3 post-model residents (n = 10) performed 350 (237-408) PNBs, 107 (92-123) spinal anesthetics, and 233 (221-241) epidural anesthetics (P < 0.0001). All results are reported as median (interquartile range). We conclude that our new teaching model using our CA-3 residents as block residents in the preoperative area has increased their clinical exposure to PNBs. IMPLICATIONS: Inadequate exposure to peripheral nerve blocks has been a national problem. A teaching model instituted at Duke University Health System has resulted in a fourfold increase in exposure to peripheral nerve blocks compared with the national averages.     

Glomerular size and global glomerulosclerosis in normal Caucasian donor kidneys: effects of aging and gender

BACKGROUND: To assess the effects of aging and gender on glomerular size and global glomerulosclerosis (GS) and evaluate the relationship between glomerular size and GS in normal Caucasian donor kidneys. METHODS: All baseline graft biopsies between 1990 and 1998 were reviewed and sections with tissues containing at least 15 glomeruli were selected for morphometric analyses using a Digital Imaging Analyzer. Glomerular volumes (GV) were measured using the maximal profile area (MPA) method. The frequency of glomeruli with totally sclerotic lesions representing degree of global GS was expressed as a percentage of total number of glomeruli counted. RESULTS: 102 donor specimens (M/F, 46/56; mean age, 37.4 +/- 17.3 yrs) were analyzed showing mean MPA of 27.8 +/- 6.6 (x 10(-3)mm2), mean GV of 3.6 +/- 1.2 (x 10(6)microm3) and mean GS% of 6 +/- 10%. GV was increased with increasing age (r2 = 0.32, p < 0.0001). There was a progressive increase in glomerular size between infancy and adolescence (2-18 years old). The rate of MPA growth over childhood appeared to be linear (n = 13, r2 = 0.66, p = 0.0004). However, MPA increased with age at a slower rate (n = 99, r2 = 0.66, p = 0.0004) in adults (excluding data for patients < 18 years) than in infancy and adolescence. There wasn't significant gender difference in GV. Age (r = 0.47, p < 0.0001) and MPA (r = 0.31, p < 0.05) were both positively correlated with global GS. CONCLUSIONS: 1. Aging contributes to enlargement of glomerular size and global GS. 2. Gender had no significant effect on glomerular size. 3. Enlargement of glomerular size was associated with global GS in normal Caucasians.     

Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease

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Sympathetic Neural Adaptation to Hypocaloric Diet With or Without Exercise Training in Obese Metabolic Syndrome Subjects

OBJECTIVE

Sympathetic nervous system (SNS) overactivity contributes to the pathogenesis and target organ complications of obesity. This study was conducted to examine the effects of lifestyle interventions (weight loss alone or together with exercise) on SNS function.

RESEARCH DESIGN AND METHODS

Untreated men and women (mean age 55 ± 1 year; BMI 32.3 ± 0.5 kg/m²) who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated to either dietary weight loss (WL, n = 20), dietary weight loss and moderate-intensity aerobic exercise (WL+EX, n = 20), or no treatment (control, n = 19). Whole-body norepinephrine kinetics, muscle sympathetic nerve activity by microneurography, baroreflex sensitivity, fitness (maximal oxygen consumption), metabolic, and anthropometric measurements were made at baseline and 12 weeks.

RESULTS

Body weight decreased by −7.1 ± 0.6 and −8.4 ± 1.0 kg in the WL and WL+EX groups, respectively (both P < 0.001). Fitness increased by 19 ± 4% (P < 0.001) in the WL+EX group only. Resting SNS activity decreased similarly in the WL and WL+EX groups: norepinephrine spillover by −96 ± 30 and −101 ± 34 ng/min (both P < 0.01) and muscle sympathetic nerve activity by −12 ± 6 and −19 ± 4 bursts/100 heart beats, respectively (both P < 0.01), but remained unchanged in control subjects. Blood pressure, baroreflex sensitivity, and metabolic parameters improved significantly and similarly in the two lifestyle intervention groups.

CONCLUSIONS

The addition of moderate-intensity aerobic exercise training to a weight loss program does not confer additional benefits on resting SNS activity. This suggests that weight loss is the prime mover in sympathetic neural adaptation to a hypocaloric diet.The metabolic syndrome (MetS) is an increasingly prevalent multidimensional risk factor for cardiovascular disease and type 2 diabetes (1). Its etiology is complex and incompletely understood, but thought to involve the interplay between metabolic susceptibility, lifestyle factors, and the acquisition of excess visceral adiposity (2). Scientific studies performed over the last 2 decades strongly support the relevance of the sympathetic nervous system (SNS) in both the pathogenesis and target organ complications of MetS obesity (3).Several indexes of SNS activity, such as urinary norepinephrine excretion, norepinephrine spillover from sympathetic nerves, and postganglionic muscle sympathetic nerve activity (MSNA) are increased in subjects with MetS, even in the absence of hypertension (4–7). Among the adiposity indexes, abdominal visceral fat is most strongly associated with elevated MSNA (8). Because of the bidirectional relationship between sympathetic activation and insulin resistance, much debate has focused on their chronology. Prospective studies with 10–20 years follow-up indicate that elevated plasma norepinephrine concentration (9) and sympathetic reactivity (10) precede and predict future rise in BMI and development of insulin resistance. Although seemingly counterintuitive, sympathetic activation may be causally linked to obesity via β-adrenoceptor desensitization (11) and insulin resistance (12,13). In established obesity, metabolic, cardiovascular (baroreflex impairment), and medical conditions (obstructive sleep apnea) contribute significantly to sympathetic neural drive and further aggravate insulin resistance, hence establishing a vicious cycle (3,7). Chronic sympathetic activation is associated with an increased prevalence of preclinical cardiovascular and renal changes that are recognized predictors of adverse clinical prognosis (3,14,15).Weight loss and exercise are recommended as first-line treatments for MetS. The Diabetes Prevention Program and the Oslo Diet and Exercise Study have shown the marked clinical benefits of intensive lifestyle intervention on the resolution of the MetS (16,17). Individually, both weight loss (5) and exercise training (18,19) cause sympathoinhibition and improvement in MetS components. We have previously reported that moderate weight loss (7% of body weight) by diet alone is accompanied by reductions in whole-body norepinephrine spillover and MSNA and improvement in spontaneous cardiac baroreflex function in middle-aged MetS subjects (5). Because exercise is often added to energy restriction in the treatment of obesity, it is pertinent to clarify its additive benefits. Augmented improvements in metabolic, anthropometric, and cardiovascular parameters have been observed after combined exercise training and dietary weight loss in some (17,20,21), but not other studies (22), and there are limited data regarding their combined effect on sympathetic activity (23). Exercise training may potentially augment weight loss induced sympathoinhibition by promoting a greater loss of fat relative to lean mass (20,21), by further improvement in insulin sensitivity (24) and reduction in plasma leptin concentration (21), and by potentiation of baroreceptor sensitivity (18).The present study was conducted to 1) test the hypothesis that weight loss by combined hypocaloric diet and aerobic exercise training would be associated with greater sympathoinhibition and improvement in MetS components than hypocaloric diet alone and 2) to examine the interrelationships between reduction in sympathetic tone and concurrent changes in anthropometric, metabolic (insulin sensitivity, plasma leptin concentration), and cardiovascular parameters. A moderate-intensity bicycle riding protocol was chosen as the exercise intervention, based on an earlier study that demonstrated attenuation in whole-body and renal norepinephrine spillover rates with this regimen in healthy men (19).